title: Serum autoantibodies recognizing 5-hydroxymethyl-2'-deoxyuridine, an oxidized DNA base, as biomarkers of cancer risk in women.
abstract: Human sera contain anti-5-hydroxymethyl-2'-deoxyuridine (HMdU; an oxidized thymidine) autoantibodies (aAbs), which are significantly higher in chronic inflammatory diseases. The intent of this study was to establish whether anti-HMdU aAbs can serve as predictors of breast and colorectal cancer risk. Sera of 169 women were analyzed by ELISA. Women healthy at blood donation but who were diagnosed 0.5-6 years later with breast or colorectal cancer exhibited significantly increased anti-HMdU aAbs over the age-matched controls (P = 0.028 and P < 0.001, respectively). Subjects diagnosed with rectal cancer had the highest levels of anti-HMdU aAbs (44.80 +/- 11.50; n = 6) in comparison to colon (29.03 +/- 2.49; n = 33) and breast (35.86 +/- 8.55; n = 9) cancers. Individuals with benign breast disease also had elevated anti-HMdU aAb (35.12 +/- 8.77; n = 10), with a borderline statistical significance (P = 0.095), whereas those with benign gastrointestinal tract diseases had those titers (30.95 +/- 3.64; n = 8) significantly increased (P < 0.02). Anti-HMdU aAb levels in subjects with a family history of any cancer (23.57 +/- 2.86; n = 55) did not significantly differ from those of the controls (19.41 +/- 2.90; n = 48), but women with a family history of breast cancer (two primary relatives or one with a bilateral disease) showed increased levels (34.48 +/- 8.16; n = 8; P = 0.024). Ps for linear trend of age-adjusted odds ratios were 0.049 for breast and < 0.001 for colorectal cancers. Anti-HMdU aAb titers showed a remarkable stability over a period of 6 years, with a low (14%) intraindividual variance. Thus, elevated anti-HMdU aAb titers may be an early signal of cancer risk, because they were significantly increased in otherwise healthy women who had a family history of breast cancer; in those who had benign breast disease or benign gastrointestinal tract diseases; and, most importantly, in those who at 0.5-6 years after the initial blood donation developed breast or colorectal cancer.
authors.affiliation: Department of Environmental Medicine, and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York 10016, USA. krystyna.frenkel@nyu.edu
authors.forename: K
authors.initials: K
authors.lastname: Frenkel
authors.forename: J
authors.initials: J
authors.lastname: Karkoszka
authors.forename: T
authors.initials: T
authors.lastname: Glassman
authors.forename: N
authors.initials: N
authors.lastname: Dubin
authors.forename: P
authors.initials: P
authors.lastname: Toniolo
authors.forename: E
authors.initials: E
authors.lastname: Taioli
authors.forename: L A
authors.initials: LA
authors.lastname: Mooney
authors.forename: I
authors.initials: I
authors.lastname: Kato
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D012907:Smoking; D013936:Thymidine / Q000031:analogs & derivatives* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; C018080:5-hydroxymethyl-2'-deoxyuridine; D013936:Thymidine